Author Reply: GFR, Race, and Implications
Authors: Cynthia Delgado
Journal: Journal of the American Society of Nephrology (2023)

Thank you for your interest in this work and raised questions in your letter1 concerning the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation and the recent work by Diao and colleagues titled "National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations."2 I would like to reassure you that the National Kidney Foundation - American Society of Nephrology (NKF-ASN) Task Force did extensively examine the clinical effect of each of the 26 kidney function estimation approaches evaluated before and not after its final recommendation. The charge of the NKF-ASN Task Force was to examine the inclusion of race in the estimation of GFR and associated implications.3 A consideration of the multiple social and clinical implications of the 26 approaches evaluated was imperative to this charge. We examined both unpublished and published evidence and heard testimony from 90 subject matter experts on the potential consequence to each eGFR approach, an undertaking that required hundreds of hours and took nearly 2 years. We did simulation analyses using National Health and Nutrition Examination Survey data to examine the potential clinical effect on a myriad of issues including potential consequences to medication initiation, discontinuation and dosing, clinical trial eligibility, CKD population tracking, and clinical decision making in general medical and nephrology care. Given that the charge of the task force was to specifically examine the use of Black race, the scope of the simulation analysis was focused on whether individuals were Black or non-Black. These simulations were used to evaluate the effect of changing from the CKD-EPI 2009 recommended approach which included the Black race variable to each of the approaches under Task Force evaluation.3 We acknowledged in this work the need for ongoing research to better understand the effect of these approaches on a more diverse US population and the need for eGFR approaches that are not sensitive to social and demographic factors. The work published by Diao and colleagues is a response to this call, extending the analysis undertaken by the Task Force to include an evaluation on the potential clinical implication among individuals who self-identify from other racial and ethnic groups. In this work, the effect on recommended clinical care was examined comparing the two most commonly used methods for kidney function estimation, 2006 Modification of Diet in Renal Disease (MDRD) and the 2009 CKD-EPI equations, with the 2021 CKD-EPI creatinine-based equations. Approaches in GFR reporting are not uniform across the United States.4 Most laboratories still use the 2006 MDRD equation, an approach that is no longer recommended. This work adds important information on the additional clinical ramifications and the risk for potentiating health disparities with its ongoing use. The simulation analysis by Diao and colleagues is a substantial contribution, filling other gaps in knowledge with a more granular examination of additional clinical decisions not examined by the NKF-ASN Task Force. Interestingly, the observed difference between 2009 CKD-EPI and 2021 CKD-EPI approaches on examined implications among Black and non-Black adults is in alignment with Task Force findings and the studies of others. For instance, although observed change in CKD diagnosis was large, the difference in the number of nephrologist referrals among both Black and non-Black adults was relatively small. Indeed, translating population-based differences to individualized care and for drug dosing in particular is a challenge. The authors acknowledged that the work presented is a simulation analysis and, therefore, may not reflect actual changes in medication dosing patterns. To address challenges and potential imprecisions with the application of population-based estimates, particularly with medication adjustments, both the authors and the NKF-ASN Task Force are in agreement. We emphasized the importance of clearance measurements as confirmatory testing when needed and the consideration of patient-specific–related factors for clinical decision making. For instance, for individuals who may fall outside the range of the standardized body surface area used in GFR estimation, further drug dosing considerations using nonindexed eGFR values may be warranted.5 The work of Diao and colleagues among others, fills critical gaps in knowledge that are crucial to help eliminate disparities in health and health care delivery among the 37 million US adults who are living with CKD and the millions more living with diabetes, hypertension, heart disease, and obesity who are at increased risk. Disclosures C. Delgado reports Advisory or Leadership Role: Glaxo Smith Kline, GUIDE-US Renal Anemia Council (paid). Funding None.